5589252 SYSTEMATIC LITERATURE REVIEW OF HEALTH-RELATED QUALITY OF LIFE BURDEN IN PATIENTS ACROSS THE SPECTRUM OF THALASSEMIA
Authors: K.M. Musallam, L. Vinals, K. Gilroy, M. Rizzo, C. Tam, L. Lombard
Journal: HemaSphere (2023)

Background: Recent systematic literature reviews (SLRs) have highlighted the health-related quality of life (HRQoL) burden in transfusion-dependent thalassemia (TDT), particularly β-thalassemia (β-thal). However, less is known about HRQoL in non–transfusion-dependent thalassemia (NTDT) and alpha-thalassemia (α-thal). Aims: To conduct an SLR on the real-world HRQoL burden across the spectrum of thalassemia and report evidence gaps. Methods: Searches (Jan 2010 to Sep 2021) were conducted in MEDLINE, Embase, Cochrane Database of Systematic Reviews, Health Technology Assessment Database, NHS Economic Evaluation Database, and EconLit for real-world studies reporting on HRQoL and utilities in adult and pediatric patients with thalassemia. Conference abstracts from Jan 2017 to Sep 2021 were also searched. References were screened by two independent reviewers, and HRQoL data were extracted by one reviewer and validated by another. Results were grouped by genotype (β-thal/α-thal) and transfusion phenotype (TDT/NTDT). Results: A total of 2,548 records were screened at title/abstract and 448 at full text. 126 publications from 116 unique studies were included and data extracted. Most evidence was published since 2015 (95/126) and sample sizes of study populations ranged from 22 to 1240. Most TDT/NTDT studies were conducted in β-thal (84/126); 10 were in mixed α-thal and β-thal, of which 2 reported data separately for Hemoglobin H disease (HbH) pediatric patients; the remaining studies did not specify the thalassemia genotype. HRQoL was significantly poorer in TD β-thal adult or adult/pediatric patients compared with healthy controls across the majority of domains. Among TDT patients, HRQoL also tended to decrease with increasing age. The burden associated with pediatric TD β-thal also impacts caregivers, with one study reporting significantly reduced HRQoL compared with healthy controls (p<0.001). In NTD β-thal patients, 2 studies identified significantly worse PedsQL scores in nearly all domains compared with healthy controls. Across studies in adult or mixed adult/pediatric patients, HRQoL (as measured by SF-36) tended to be poorer among NTDT (β-thal intermedia) compared with TDT (β-thal major) patients. For example, a prospective study found significantly lower SF-36 mental component scores at baseline in adult NTDT vs. TDT (mean [standard deviation (SD)]: 47.4 [8.4] vs. 51.6 [7.2]; p=0.009). While in pediatric patients, there was a pattern for poorer HRQoL burden in TDT vs. NTDT. TD α-thal and β-thal pediatric patients had similar total and subdomains of PedsQL scores, except for physical functioning, whereby homozygous β-thal patients had the best HRQoL, followed by HbH patients, with β-thal/Hb E patients demonstrating the greatest HRQoL burden (mean [SD]: 76.52 [15.23] vs. 61.16 [18.39] vs. 56.88 [17.17], p=0.008). Another study did not find differences in any PedsQL subdomain between HbH, β-thal, and homozygous β-thal (TDT and NTDT, patients 5-18 years; N=315). Conclusion: This SLR highlights the negative impact on HRQoL across the spectrum of thalassemia. Adding to previous SLRs, it shows limited evidence is available for NTDT patients; however, studies suggest that HRQoL burden may be worse in NTDT than TDT adult patients. Characterizing the HRQoL burden of α-thal is a clear evidence gap. High-quality, real-world studies in NTDT and α-thal are needed to better understand the HRQoL burden and the potential impact of new treatments on HRQoL. References 1. Betts et al, Clin Ther. 2020 Feb;42(2):322-337 2. Turner et al, Blood. 2019;134(Suppl 1):5786